Project Summary Recently, the use of focused ultrasound (FUS) to treat cancer, Alzheimer?s, Parkinson?s disease and other maladies has received much attention. New FUS applications for ablation, hyperthermia or mechanical tissue perturbation are promising. FUS?s importance to clinical medicine will continue to rise. While thermal-based FUS can be monitored in near real time using MRI thermometry, mechanically-based FUS applications require an alternative form of monitoring. Controlling the focus of a FUS source and its location in a tissue during exposure is an important aspect of mechanically-based FUS therapy. For example, tissue motion can shift the location of the FUS focus relative to the treatment region. Therefore, it is important to continuously visualize the FUS focal region and it is medically significant to develop a noninvasive imaging technique to meet this need that is low cost, portable, robust to tissue motion and real time. With these goals in mind, we propose to develop and demonstrate a real-time imaging capability to visualize the FUS beam in situ placing the therapy beam in the context of tissue anatomy. Specifically, we will develop a passive detection technique using an ultrasonic array co-aligned with the FUS source. The listening array will collect signals scattered from the FUS beam in the field. The passive action of the array will be combined with an active action of the array to create a registered B-mode image. We will use delay and sum beam focusing techniques to map out in real time the location and extent of the FUS beam and superimpose the beam visualization on the registered B-mode image. When successfully demonstrated, this would offer a real-time feedback capability to a physician using mechanically-based FUS therapy with the feedback coming from a conventional ultrasound machine. The costs associated with operating a portable and real-time ultrasonic system would be substantially less than required for an MRI device. Furthermore, the accessibility of using ultrasound to provide monitoring and feedback would be greatly increased and would further promote FUS as an alternative for noninvasive therapy. In this proposal we will accomplish our overall goal of developing a real-time in vivo FUS field visualization technique through two specific aims. The first aim is to develop and demonstrate the capability to visualize a FUS beam in real time in situ superimposed on a B- mode image of the tissue structure. We will demonstrate these capabilities in tissue-mimicking phantoms, ex vivo tissue samples and in an in vivo therapy application. The second specific aim is to improve image quality by incorporating intensity variation corrections from registered B-mode images. Variations in the FUS beam image due to differences in scattering within the beam will be accounted for by quantifying the scattered intensity from co-registered B-mode images and using these values to adjust the intensity variations in the FUS beam visualization.